Neuropsychiatric Disease Modeling Using Human Pluripotent Stem Cells

There is yet no satisfying evidence-based biological mechanism for any psychiatric disorder, likely due to the extraordinary complexity of the brain and the difficulties inherent in studying human neurophysiology. Towards the goal of establishing standardized methods for investigating the pathophysiology of human brain disorders, we have developed novel state-of-the-art methods for differentiating physiologically active three-dimensional (3D) neuronal networks from human patient-derived induced pluripotent stem cells, offering the unique opportunity to investigate the molecular and cellular pathophysiology of disease initiation and progression. In my lecture, I will discuss the implementation of this methodology and the electrophysiological properties of the resulting neuronal networks. Moreover, I will describe the successful application of this approach for revealing fundamental insights into the neurobiology of schizophrenia using a family-based design supported by next-generation sequencing.